Non-small-cell lung cancer: reirradiation for loco-regional relapse previously treated with radiation therapy

Background We evaluated the efficacy and toxicity of reirradiation for patients with loco-regional relapse of non-small-cell lung cancer after radiation therapy.Methods Between 1992 and 2002, 19 patients with loco-regional relapse underwent reirradiation. The median interval between the initial irradiation and reirradiation was 16 months, with a range of 5 to 60 months. The prescribed dose of reirradiation was 50 Gy in 25 fractions over 5 weeks for 18 patients and 60 Gy in 30 fractions over 6 weeks for 1 patient.Results Five patients could not receive the prescribed dose of reirradiation. The response rate was 43% among the 14 patients who received the prescribed dose of reirradiation. The overall 1-year and 2-year Kaplan-Meier survival rates were 26% and 11%, respectively, and the median survival time was 7.1 months. The median survival times associated with intervals between the initial irradiation and reirradiation of less than 12 months, 12–18 months, and more than 18 months were 2.1, 7.1, and 11.5 months, respectively. There were significant differences in survival between patients with an interval of less than 12 months and those with an interval of 12–18 months, and between those with an interval of less than 12 months and those with an interval of more than 18 months (generalized Wilcoxon method; P < 0.05 for both). Grade 3 radiation pneumonitis and grade 2 radiation esophagitis occurred in 1 and 3 patients, respectively.Conclusion Reirradiation is considered to contribute to salvage in selected patients with relapsed non-small-cell lung cancer. Patients with a long interval after the initial irradiation are good candidates for reirradiation. On the other hand, patients with Eastern Cooperative Oncology Group (ECOG) performance status 3 were not goodcandidates.     

Post-prostatectomy radiation therapy for locally recurrent prostate cancer

Introduction: Approximately 15–30% of men with localized prostate cancer will experience biochemical recurrence (BCR) after radical prostatectomy. Postoperative radiation therapy is used in men with adverse pathological features to reduce the risk of BCR or with curative intent in men with known BCR. In this study, we review the evidence for the adjuvant and salvage radiation therapy after radical prostatectomy.

Areas covered: A literature review of the Medline and Embase databases was performed. The search strategy included the following terms: prostate cancer, adjuvant radiotherapy, salvage radiotherapy, radical prostatectomy, biochemical recurrence, and prostate cancer recurrence. Prospective randomized trials for the adjuvant radiotherapy and observational studies supporting salvage radiotherapy were included for discussion.

Expert commentary: As postoperative radiotherapy is associated with non-trivial risks of acute and long-term toxicity and given the absence of compelling data supporting adjuvant over early salvage radiotherapy, the authors advocate, with rare exceptions, close observation and timely (early) salvage radiotherapy for patients with BCR and long life expectancy. Adjuvant radiotherapy may be considered in patients at high-risk for recurrence. Observation is appropriate in patients with limited life expectancy and/or absence of adverse features.     

Reirradiation of locally recurrent rectal cancer: A systematic review

Background: Many patients with rectal cancer receive radiotherapy as a component of primary multimodality treatment. Although local recurrence is infrequent, reirradiation may be needed to improve resectability and outcomes. This systematic review investigated the effects of reirradiation in terms of feasibility, toxicity, and long-term outcomes. Methods: A Medline, Embase and Cochrane search resulted in 353 titles/abstracts. Ten publications describing seven prospective or retrospective studies were included, presenting results of 375 patients reirradiated for rectal cancer. Results: Median initial radiation dose was 50.4 Gy, median 8–30 months before reirradiation. Reirradiation was mostly administered using hyperfractionated (1.2–1.5 Gy twice-daily) or 1.8 Gy once-daily chemoradiotherapy. Median total dose was 30–40 Gy to the gross tumour volume with 2–4 cm margins. Median survival was 39–60 months in resected patients and 12–16 months in palliative patients. Good symptomatic relief was reported in 82–100%. Acute toxicity with diarrhoea was reported in 9–20%, late toxicity was insufficiently reported. Conclusions: Reirradiation of rectal cancer to limited volumes is feasible. When curative resection is possible, the goal is radical resection and long-term survival, and hyperfractionated chemoradiotherapy should be preferred to limit late toxicity. Reirradiation yielded good symptomatic relief in palliative treatment.     

Intraoperative radiation therapy for locally advanced recurrent rectal or rectosigmoid cancer

Recurrent rectal or rectosigmoid cancer is a difficult therapeutic problem. A treatment program of external beam irradiation, surgery, and intraoperative irradiation has been used for 41 patients. The 5-year actuarial local control and disease-free survival of all 41 patients was 30% and 16%, respectively. Subset analysis demonstrated differences in outcome by extent of surgical resection. The 5-year actuarial local control and disease-free survival of 27 patients undergoing complete resection was 47% and 21%, respectively. By contrast, the outcome of 14 patients undergoing partial resection was poor, with a 5-year actuarial local control and survival of 21% and 7%, respectively. Late complications included soft tissue or peripheral nerve injury, with many of these resolving within 4–18 months. Local control and disease-free survival rates are favorable in comparison with the results achieved by aggressive surgery. Patients who achieve a gross total resection at intraoperative irradiation have a markedly better prognosis than that of patients with residual gross disease. © 1995 Wiley-Liss, Inc.     

调强（IMRT）放疗复发性鼻咽癌初期报道

目的观察调强放疗复发性鼻咽癌剂量分布及可行性.方法1999年6月-2000年8月,10例病理确诊局部复发的鼻咽癌接受了调强放疗.复发距初次治疗中位时间25(14-50)个月.首程放疗均采用单纯外放射,中位剂量52天共69Gy/35次.调强放疗通过NOMOS公司PEACOCK系统完成.再程放疗处方剂量4周共57Gy/19次.结果除部分患者有体重下降和轻度口腔粘膜反应外,所有患者均能耐受这一治疗.即期疗效完全缓解6例,部分缓解4例.2例局部再次复发,1例肺转移,2例病人死亡.全组中位生存时间14个月.全组中位计划靶体积(PTV)95.8(60-134)cm3.PTV剂量分布平均25-28天59.65±2.47Gy/19次;均匀指数(最大剂量/处方剂量)1.18±O.06,95%PTV的接受剂量为53.2±1.36Gy以上,低于95%处方剂量的体积(5.4±1.2)%.危险组织器官(OAR)平均剂量均值脊髓(9.46±5.23)Gy;脑干(20.24±3.55)Gy;腮腺(18.53±5.30)Gy(左),(19.68±6.21)Gy(右);晶体(2.11±0.65)GY(左),(2.94±O.57)Gy(右);视交叉(12.34±2.47)Gy;视神经(13.14±3.65)Gy(左),(17.65±3.21)Gv(右).结论该治疗能被患者耐受,即期疗效理想,有较好物理剂量分布.     

Reirradiation, surgery and IORT for recurrent rectal cancer in previously irradiated patients

A total of 11 patients with recurrent rectal cancer who had been previously irradiated were treated with preoperative reirradiation (median dose 30Gy), surgery and IORT. This treatment was related with high morbidity, a short pain-free survival (5 months) and poor local control (27% after 3 years), although some patients have long-term distant control and survival.     

三维适形放疗联合化疗治疗局部晚期和术后复发性直肠癌

目的：探讨局部晚期和术后复发性直肠癌三维适形放射治疗（3D—CR）联合化疗的临床疗效。方法：30例局部晚期和术后复发性直肠癌采用常规放射治疗至40Gy，再予后程适形放疗加化疗。适形放疗25Gy-30Gy，肿瘤总量65Gy-70Gy；化疗采用奥沙利铂130mg／m^2，d1，亚叶酸钙100mg／m^2，d1-5,5-氟脲嘧啶500mg／m^2，d1-5。结果：患者有效率为90％；12、24、36月生存率分别为83．3％，60％，40％；12、24、36月局部控制率分别为90％，83．3％，56．7％。胃肠道反应、骨髓抑制、放射性直肠炎、放射性膀胱炎为主要副反应，多为1—2级。结论：三维适形放疗联合化疗可提高局部晚期和术后复发性直肠癌的控制率和生存率。     

Salvage radiation therapy for locally recurrent nasopharyngeal carcinoma

Purpose: To study the treatment outcome in patients with locally recurrent nasopharyngeal carcinoma (NPC) and to explore whether a combination of high-dose-rate (HDR) intracavitary brachytherapy and external beam radiation therapy (ERT) could improve the therapeutic ratio.

Methods and Materials: Ninety-one patients with nonmetastatic locally recurrent NPC who were treated with curative intent during the years 1990–1999 were retrospectively analyzed. Eighty-two patients had histologically proven carcinoma. The remaining 9 had clinical and imaging features suggestive of local recurrence. The Ho’s T-stage distribution at recurrence (rT) was as follows: rT1–37, rT2–14, rT3–40. Total equivalent dose (TED) was calculated by the linear–quadratic formula without a time factor correction. For those treated by combined-modality treatment (CMT), the TED was taken as the summation of the equivalent dose by ERT and the absolute dose delivered to floor of the sphenoid by brachytherapy. Eight patients were treated solely with brachytherapy, all receiving 24–45 Gy in 3–10 sessions. Forty-one patients were treated with ERT alone receiving a median TED of 57.3 Gy (range, 49.8–62.5 Gy). Forty-two patients were treated by CMT with a median equivalent dose of 50 Gy (range, 40–60 Gy) given by ERT and 14.8 Gy by brachytherapy (range, 3–29.6 Gy). Multivariate analyses were performed using the Cox regression proportional hazards model.

Results: The 5-year actuarial overall survival rate, disease specific survival rate and local failure-free survival (LFFS) rate for the whole group were 30%, 33.3% and 37.8%, respectively. The 3-year LFFS rates of rT1, rT2, and rT3 diseases were 64%, 61.5%, and 18.4%, respectively (p = 0.001).

Of the 8 patients treated with brachytherapy alone, 4 failed locally. Further analyses were concentrated on the ERT (41 patients) and CMT (42 patients) groups. The 3-year LFFS rates of rT1, rT2, and rT3 diseases were 66.7%, 66.7%, and 18.4%, respectively (p = 0.0008). Better local control for patients who received a TED of 60 Gy or greater was shown. The corresponding 3-year LFFS rates were 29% and 60% (p = 0.0004). Subgroup analysis on the ERT and CMT groups showed a 3-year LFFS rate of 33.5% and 57% (p = 0.003). ERT group had an excess of patients with rT3 disease. Further analysis was performed on the rT1–2 patients showing a trend toward improvement in local control in favor of the CMT group (3-year LFFS rates: CMT, 71.7%; ERT, 54%; p = 0.13). Multivariate analyses showed that rT stage (p = 0.002) and TED (p = 0.01; HR, 0.93; 95% confidence interval, 0.88–0.98) remained significant.

The 5-year major and central nervous system (CNS) complication-free rates were 26.7% and 47.8%. The following factors were found to be significant on univariate analyses for both complications in the ERT and CMT groups: (1) Modality of treatment: more complications with ERT group; and (2) rT stage. Multivariate analyses showed that the rT stage was significant for predicting the occurrence of major (p = 0.004) and CNS complications (p = 0.04).

Conclusion: For rT1–2 local recurrences, CMT with at least 60 Gy TED is recommended. The high incidence of major late complications is of serious concern. Ways of improving the local control of Ho’s rT3 disease and reducing the risk of late complications should be explored.     

Intraoperative radiation therapy for locally advanced recurrent rectal or rectosigmoid cancer.

BACKGROUND AND PURPOSE: To update and summarize the experience at the Massachusetts General Hospital of a treatment program of high-dose preoperative irradiation, surgical re-resection, and intraoperative radiation therapy (IORT) as a salvage treatment for patients with recurrent rectal or rectosigmoid carcinoma. PATIENTS AND METHODS: From June 1978 to February 1997, the records of 69 patients with locally recurrent rectal carcinomas or rectosigmoid carcinomas without metastases referred for consideration of IORT were reviewed. Forty-nine patients received IORT and local control and disease-free survival curves were calculated using the actuarial method of Kaplan-Meier. RESULTS: The 5-year overall survival, local control and disease-free survival rates of 49 patients receiving IORT were 27, 35, and 20%, respectively. Thirty-four patients who underwent a macroscopic complete resection had a significantly better 5-year overall survival than the remaining 15 patients with gross residual disease (33 vs. 13%, P=0.05, log rank). For those patients, local control and disease-free survival rates were 46 and 27%, respectively. Patients with a microscopic complete resection had a superior 5-year overall survival than partially resected patients (40 vs. 14%, P=0.0001, log rank). Chemotherapy had no significant influence on overall or disease-free survival. CONCLUSION: The current analysis shows the importance of a microscopic complete resection in a multi-modality approach with IORT for survival and local control. Salvage is rare for patients undergoing subtotal resection.     

A case of recurrent gastric cancer successfully treated with radiation therapy

We report a case of recurrent gastric cancer that was effectively controlled with radiation therapy. A 63-year-old man underwent total gastrectomy, cholecystectomy and D2 dissection in February 2006 for early gastric cancer in the upper third area that was diagnosed with papillary adenocarcinoma and Stage IA (T1 (SM), N0, H0, P0, CY0, M0). He underwent lateral segmentectomy of the liver for liver metastasis of S2/3. He suffered from No. 12 lymph node(LN)metastasis in February 2009, so CPT-11, next to S-1, was administered. Portal tumor thrombosis (PTT) and liver S8 metastasis were observed in September 2009. First, chemoradiotherapy (CRT) ( S-1 80 mg/body+total of 65 Gy per 26 Fr) for #12 LN and PTT was performed and, in turn, stereotactic radiation therapy (SRT: total of 52.8 Gy per 4 Fr) was performed. A complete response in all of tumors was noted and he was presently alive with no sign of recurrence after 19 months after CRT and SRT. Grade 3 or 4 adverse events were not recognized. It is thought that radiation therapy is one of effective treatments for localized metastasis from gastric cancer.     

EGFR inhibitors with concurrent thoracic radiation therapy for locally advanced non-small cell lung cancer

Currently, a combination of chemotherapy and radiotherapy is the standard treatment approach for locally advanced non-small cell lung cancer (NSCLC). However, the clinical outcomes are still disappointing, with the 5-year survival rate being only approximately 20%. Further improvement in treatment outcome for patients with locally advanced NSCLC will require the development of more effective combined-modality therapies. Increasing attention has focused on the integration of targeted agents into current therapies. Many preclinical studies in this area have targeted the epidermal growth factor receptor (EGFR) signaling pathway to increase radiosensitivity. The in vitro rationale for targeting EGFR and concurrent ionizing radiation is well established, but to date, rare clinical data could provide proof-of-principle. In this review article, we briefly discuss pre-clinical data and the rationale and report all the different published clinical trials focusing on efficacy and toxicity in order to clarify and to summarize the present state-of-the-art of this particular combination in NSCLC.     

Three-dimensional conformal radiation therapy for locally recurrent nasopharyngeal carcinoma

Local recurrence is a major cause of treatment failure for NPC,[1] seen in approximately 20%(30% of patients after radiation therapy with radical dose.[2(5] Retreatment for locally recurrent NPC is a real challenge, and radiation therapy is still the mainstay of retreatment modulates.[1] It was proved that conventional methods with X-ray simulation and 2-dimensional planning were not satisfactory for locally recurrent NPC. The prognosis for patients undergoing reradiation is grave,[2(4, 6(…     

Patient selection for salvage cryotherapy for locally recurrent prostate cancer after radiation therapy.

PURPOSE: Our objective was to identify clinical pretreatment factors associated with early treatment failure after salvage cryotherapy. PATIENTS AND METHODS: Between 1992 and 1995, 145 patients underwent salvage cryotherapy for locally recurrent adenocarcinoma of the prostate. Treatment failure was defined as an increasing postcryotherapy serial prostate-specific antigen (PSA) level of more than or equal to 2 ng/mL above the postcryotherapy nadir or as a positive posttreatment biopsy. We evaluated the following factors as predictors of treatment failure: tumor stage and grade at initial diagnosis, type of prior therapy, stage and grade of locally recurrent tumor, number of positive biopsy cores at recurrence, and precryotherapy PSA level. RESULTS: Among patients with a prior history of radiation therapy only, the 2-year actuarial disease-free survival (DFS) rates were 74% for patients with a precryotherapy PSA less than 10 ng/mL and 28% for patients with a precryotherapy PSA more than 10 ng/mL, P <.00001. The DFS rates were 58% for patients with a Gleason score of less than or equal to 8 recurrence and 29% for patients with a Gleason score greater than or equal to 9 recurrence, P <.004. Among patients with a precryotherapy PSA less than 10 ng/mL, DFS rates were 74% for patients with a prior history of radiation therapy only and 19% for patients with a history of prior hormonal therapy plus radiation therapy, P <.002. CONCLUSION: Patients failing initial radiation therapy with a PSA more than 10 ng/mL and Gleason score of the recurrent cancer more than or equal to 9 are unlikely to be successfully salvaged. Patients failing initial hormonal therapy and radiation therapy are less likely to be successfully salvaged than patients failing radiation therapy only.     

256例局部晚期NSCLC患者IMRT后急性症状性食管炎预测因素分析

目的 探索局部晚期NSCLC患者IMRT后急性症状性食管炎的发生率及相关预测因素。方法 2007—2011年间在本院治疗的256例未手术的Ⅲ期NSCLC患者。放疗靶区包括原发肺肿瘤及受累淋巴引流区, 中位剂量为60 Gy分30次(50~70 Gy)。109例(42.6%)接受同期化疗。放疗期间及放疗结束后3个月内出现≥2级急性食管炎(症状性食管炎)作为终点事件, 采用CTCAE3.0评估急性食管炎级别。采用Logistic回归模型对预测因素进行分析。结果 174例患者(68%)出现治疗相关的≥2级急性食管炎, 其中154例(60.2%)为2级、20例(7.8%)为3级。≥2级急性食管炎发生时的中位剂量为30 Gy (11~68 Gy)。食管V₅—V₆₀、食管平均剂量及年龄是≥2级急性食管炎的预测因素(P=0.021、0、0.010), 其中高龄是保护性因素;食管V₅₀—V₆₀、同期化疗、体重指数是≥3级急性食管炎的预测因素(P=0.010、0.003、0.019), 其中高体重指数是保护性因素。结论 局部晚期NSCLC患者IMRT后食管V₅₀—V₆₀和同期化疗是≥3级急性食管炎的预测因素, 食管V₅₀对预测≥2级、≥3级急性食管炎都有较高价值。     

Intraoperative irradiation for locally recurrent colorectal cancer in previously irradiated patients

Purpose: Information in the literature regarding salvage treatment for patients with locally recurrent colorectal cancer who have previously been treated with high or moderate dose external beam irradiation (EBRT) is scarce. A retrospective review was therefore performed in our institution to determine disease control, survival, and tolerance in patients treated aggressively with surgical resection and intraoperative electron irradiation (IOERT) ± additional EBRT and chemotherapy.

Methods and Materials: From 1981 through 1994, 51 previously irradiated patients with recurrent locally advanced colorectal cancer without evidence of distant metastatic disease were treated at Mayo Clinic Rochester with surgical resection and IOERT ± additional EBRT. An attempt was made to achieve a gross total resection before IOERT if it could be safely accomplished. The median IOERT dose was 20 Gy (range, 10–30 Gy). Thirty-seven patients received additional EBRT either pre- or postoperatively with doses ranging from 5 to 50.4 Gy (median 25.2 Gy). Twenty patients received 5-fluorouracil ± leucovorin during EBRT. Three patients received additional cycles of 5-fluorouracil ± leucovorin as maintenance chemotherapy.

Results: Thirty males and 21 females with a median age of 55 years (range 31–73 years) were treated. Thirty-four patients have died; the median follow-up in surviving patients is 21 months. The median, 2-yr, and 5-yr actuarial overall survivals are 23 months, 48% and 12%, respectively. The 2-yr actuarial central control (within IOERT field) is 72%. Local control at 2 years has been maintained in 60% of patients. There is a trend toward improved local control in patients who received ≥30 Gy EBRT in addition to IOERT as compared to those who received no EBRT or <30 Gy with 2-yr local control rates of 81% vs. 54%. Distant metastatic disease has developed in 25 patients, and the actuarial rate of distant progression at 2 and 4 years is 56% and 76%, respectively. Peripheral neuropathy was the main IOERT-related toxicity; 16 (32%) patients developed neuropathies (7 mild, 5 moderate, 4 severe). Ureteral narrowing or obstruction occurred in seven patients. All but one patient with neuropathy or ureter fibrosis received IOERT doses ≥20 Gy.

Conclusion: Long-term local control can be obtained in a substantial proportion of patients with aggressive combined modality therapy, but long-term survival is poor due to the high rate of distant metastasis. Re-irradiation with EBRT in addition to IOERT appears to improve local control. Strategies to improve survival in these poor-risk patients may include the more routine use of conventional systemic chemotherapy or the addition of novel systemic therapies.     

局部晚期非小细胞肺癌三维放疗后放射性肺损伤风险因素分析

目的 探讨局部晚期非小细胞肺癌(NSCLC)三维放疗后放射性肺损伤(RILT)与临床和剂量学因素的关系,以寻找RILT的可能风险因素。方法 回顾分析2001-2007年间接受三维放疗的未手术Ⅲ期NSCLC患者 253例临床和剂量学资料,采用NCI-CTC 3.0标准评估RILT级别,以放疗结束后3个月内发生的≥2级RILT作为终点事件,用Logistic回归模型分析影响RILT发生的相关因素。结果 253例中≥ 2级RILT的发生率为26.5%。单因素分析显示年龄、放疗前1 s用力呼吸体积占预测值百分比(FEV1%)、一氧化碳弥散量占预测值百分比(DLCO%)、健肺 V₅~V₁₅、患肺 V₅~V₄₀、全肺 V₅~V₅₀、患肺及全肺的平均肺剂量(MLD)与RILT的发生相关(χ²=4.46~23.99,P=0.000~0.035)。多因素分析显示全肺MLD>17.5 Gy、FEV1%≥72%是≥2级RILT的独立危险因素(χ²=17.49、9.30,P=0.000、0.002)。根据MLD和FEV1%将患者分为低危、中危、中高危和高危组,RILT的发生率分别为9.3%、24.7%、38.5%和63.6%(χ²=25.27,P=0.000)。结论 全肺MLD及放疗前FEV1%与放疗后≥2级RILT发生密切相关。基线较差的肺功能并未增加RILT风险,甚至可能具有相对较低的风险,该趋势尚需在大样本人群中进行验证。     

Reirradiation for recurrent head and neck cancer

Recurrence of head and neck cancer in a previously irradiated volume presents a challenging problem and has poor prognosis. A minority of patients are eligible for the preferred therapy, surgical resection. Systemic therapy is offered to patients with unresectable disease but offers little, if any, chance of cure. Repeat irradiation with systemic therapy is a potentially curative option. One randomized trial and several cooperative group and institutional studies support its use. Long-term disease-free survival has been observed, albeit with the risk of significant, possibly life threatening, late complications. Intensity-modulated radiotherapy has been shown to reduce toxicity and improve disease control. Novel systemic therapies and radiotherapy techniques, including stereotactic body radiotherapy, are under active study.     

复发宫颈癌再次放疗

盆腔脏器切除术是照射野内复发宫颈癌的首选治疗,但伴随着较高的死亡率并丧失盆腔脏器结构和功能.三维近距离治疗及立体定向体部放疗应用于照射野内复发宫颈癌再次放疗,提供了与盆腔脏器切除术相似的疗效、可接受的毒性反应以及保留脏器功能的机会.     

47例术后局部复发非小细胞肺癌三维适形放疗的疗效分析

背景与目的:放射治疗是不可手术非小细胞肺癌(non-small cell lung cancer,NSCLC)重要的局部治疗手段,本研究旨在探讨三维适形放射治疗(three dimensional conformal radiotherapy,3D-CRT)NSCLC术后局部复发患者的不良反应及近远期疗效.方法:回顾性分析我院47例术后局部复发NSCLC患者接受3D-CRT治疗的临床资料.全组放疗剂量中位值60 Gy(46～66 Gy),每次1.8～2.0 Gy,每周5次.36例患者接受了序贯化疗.观察放疗中的不良反应、治疗后的疾病缓解情况,Kaplan-Meier法计算生存率,并进行预后因素分析.结果:84％的患者临床症状有明显缓解.近期疗效:CR 11例,PR 26例,SD 9例,1例进展.随访截至2009年12月31日,死亡42例,存活5例.全组中位生存期15.9个月,其1、2和5年生存率分别为61.7％、36.2％和12.8％.≥2级放射性肺炎7例,其中3级2例.多因素分析发现年龄≤60岁、单纯残端复发以及放疗剂量＞60 Gy是影响生存的独立预后因素.结论:3D-CRT治疗术后局部复发NSCLC安全有效,对经选择的预期生存长的患者应给予积极治疗.